(480c) Mixing Studies with Elephant Ear Impellers: Are They Low Shear Agitators?

Ever since the 1980s when animal cells first started to become important for the production of biopharmaceuticals, there has been concern for their ?shear sensitivity'. As a result, initially, there were many attempts to find ?low shear' systems in which to grow them rather than the agitated ?submerged' fermentation vessels used for other more robust organisms. For large-scale production, airlift bioreactors were introduced, as it was perceived that they met this criterion. However, later work soon showed that the stresses associated with bursting bubbles were much more damaging to cells than those due to agitation. Fortunately, it had been shown much earlier that the surfactant, Pluronic F68, was able to prevent such damage whatever the reactor type. As a result, and perhaps also because of the inherent flexibility, the stirred bioreactor has become the bioreactor of choice for large-scale free suspension animal cell culture up to 20,000 L that are now being installed. However, there is still a belief that cells will grow better if agitation is provided by ?low shear' agitators. Recently, a particularly favoured one has been the type colloquially known as an ?elephant ears agitator.' In this presentation, a detailed analysis will be given of the flow characteristics of such an agitator using the advanced fluid dynamic measurement technique, particle imaging velocimetry (PIV). Both unaerated and aerated conditions were used at specific energy dissipation rates up to 0.1 W/kg and air flow rates of 0.01 to 0.05 vvm, which are typical for animal cell culture. In particular, the global flow field and turbulence parameters have been measured, the latter characterising ?shear sensitivity', as well as unaerated and aerated power numbers and air dispersion characteristics. These data are compared with equivalent measurements for a standard pitched blade turbine and with a Lightnin' A-315 hydrofoil agitator, which has found favour relatively recently as a ?low shear' agitator for mycelial and bacterial fermentations. The results indicate that with respect to ?shear sensitivity', all the agitators are essentially the same. A brief review of the use of other agitators for growing animal cells, including the so-called ?high-shear' Ruston turbine, will be presented. It is concluded that though different agitators may offer advantages in other ways, e.g. better bulk blending, aerated power or air dispersion characteristics, they do not do so in relation to ?shear sensitivity'.